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Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse

Amy Richardson, Victoria Ciampani, Mihai Stancu, Sherylanne Newton, Joern R. Steinert, Nadia Pilati, Bruce P. Graham, Conny Kopp-Scheinpflug, View ORCID ProfileIan D. Forsythe
doi: https://doi.org/10.1101/2021.11.02.466934
Amy Richardson
1Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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Victoria Ciampani
1Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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Mihai Stancu
2Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-University Munich, Großhaderner Strasse 2, Planegg-Martinsried, 82152 Germany
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Sherylanne Newton
1Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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Joern R. Steinert
1Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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Nadia Pilati
3Autifony S.r.l., Istituto di Ricerca Pediatrica Citta’della Speranza, Corso Stati Uniti, 35127 Padova, Italy
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Bruce P. Graham
4Computing Science and Mathematics, Faculty of Natural Sciences, University of Stirling, Stirling FK9 4LA, UK
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Conny Kopp-Scheinpflug
2Division of Neurobiology, Faculty of Biology, Ludwig-Maximilians-University Munich, Großhaderner Strasse 2, Planegg-Martinsried, 82152 Germany
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Ian D. Forsythe
1Auditory Neurophysiology Laboratory, Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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  • ORCID record for Ian D. Forsythe
  • For correspondence: idf@le.ac.uk
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Summary

Kv3 potassium currents mediate rapid repolarization of action potentials (AP), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal. Deletion of Kv3.3 (but not Kv3.1) increased presynaptic AP duration and facilitated transmitter release, which in turn enhanced short-term depression during high frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 is the presynaptic ‘delayed rectifier’, enabling short duration, precisely timed APs to maintain transmission at high frequencies and during sustained synaptic activity.

Competing Interest Statement

One author (NP) is employed by Autifony Therapeutics Ltd.

Footnotes

  • Contact information Ian D Forsythe, Email: idf{at}le.ac.uk Department of Neuroscience, Psychology & Behaviour, College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.

  • Declaration of interests One author (NP) is employed by Autifony Therapeutics Ltd. The authors have no other interests to declare.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 03, 2021.
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Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse
Amy Richardson, Victoria Ciampani, Mihai Stancu, Sherylanne Newton, Joern R. Steinert, Nadia Pilati, Bruce P. Graham, Conny Kopp-Scheinpflug, Ian D. Forsythe
bioRxiv 2021.11.02.466934; doi: https://doi.org/10.1101/2021.11.02.466934
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Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse
Amy Richardson, Victoria Ciampani, Mihai Stancu, Sherylanne Newton, Joern R. Steinert, Nadia Pilati, Bruce P. Graham, Conny Kopp-Scheinpflug, Ian D. Forsythe
bioRxiv 2021.11.02.466934; doi: https://doi.org/10.1101/2021.11.02.466934

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